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Mice lacking the proton channel Hv1 exhibit sex-specific differences in glucose homeostasis.
Pang, Huimin; Li, Jinzhi; Wang, Yuzhou; Su, Xiaomin; Gao, Yingtang; Li, Shu Jie.
Affiliation
  • Pang H; Department of Biophysics, School of Physics Science, The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin, PR China.
  • Li J; Biology Laboratory, Tianjin High School, Tianjin, PR China.
  • Wang Y; Laboratory Animal Center, College of Life Sciences, Nankai University, Tianjin, PR China.
  • Su X; Laboratory Animal Center, College of Life Sciences, Nankai University, Tianjin, PR China.
  • Gao Y; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Nankai University Affiliated Third Center Hospital, Tianjin, PR China. Electronic address: 31017014@nankai.edu.cn.
  • Li SJ; Department of Biophysics, School of Physics Science, The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin, PR China; Biomedical Research Center, Qilu Institute of Technology, Shandong, PR China. Electronic address: shujieli@nankai.edu.cn.
J Biol Chem ; 297(4): 101212, 2021 10.
Article in En | MEDLINE | ID: mdl-34547291
ABSTRACT
Sex as a physiologic factor has a strong association with the features of metabolic syndrome. Our previous study showed that loss of the voltage-gated proton channel Hv1 inhibits insulin secretion and leads to hyperglycemia and glucose intolerance in male mice. However, there are significant differences in blood glucose between male and female Hv1-knockout (KO) mice. Here, we investigated the differences in glucose metabolism and insulin sensitivity between male and female KO mice and how sex steroids contribute to these differences. We found that the fasting blood glucose in female KO mice was visibly lower than that in male KO mice, which was accompanied by hypotestosteronemia. KO mice in both sexes exhibited higher expression of gluconeogenesis-related genes in liver compared with WT mice. Also, the livers from KO males displayed a decrease in glycolysis-related gene expression and an increase in gluconeogenesis-related gene expression compared with KO females. Furthermore, exogenous testosterone supplementation decreased blood glucose levels in male KO mice, as well as enhancing insulin signaling. Taken together, our data demonstrate that knockout of Hv1 results in higher blood glucose levels in male than female mice, despite a decreased insulin secretion in both sexes. This sex-related difference in glucose homeostasis is associated with the glucose metabolism in liver tissue, likely due to the physiological levels of testosterone in KO male mice.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Blood Glucose / Sex Characteristics / Gluconeogenesis / Glycolysis / Ion Channels / Liver Limits: Animals Language: En Journal: J Biol Chem Year: 2021 Document type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Blood Glucose / Sex Characteristics / Gluconeogenesis / Glycolysis / Ion Channels / Liver Limits: Animals Language: En Journal: J Biol Chem Year: 2021 Document type: Article